Ion sensitive field effect transistors (ISFETs) are well known as pH sensitive biosensors, and are also capable of being used for biochemical sensing where the sensing gate surface is functionalized with a material for selective recognition of a target species. Arrays of ISFETs may be utilized for the multiplexed detection of multiple different species. Array-based measurement may also be used to measure a single quantity multiple times, thus minimizing errors in detection.
A known structure for ISFET sensing is the extended gate ISFET as described in Smith, J., Shah, S., Goryll, M., Stowell, J. and Allee, D., “Flexible ISFET Biosensor Using IGZO Metal Oxide TFTs and an ITO Sensing Layer”, IEEE Sensors J. 14(4) pp. 937-938 (2014) (Smith et al.). According to the extended gate principle, the physical gate of the transistor is connected to a sensing electrode. The sensing electrode is a conductor (ITO) which is typically larger than the transistor gate. An extended gate sensor is described in “Smith et al”. The drain-source and reference bias voltages are maintained constant and the current through the devices is measured as a function of time. This current is a function of the pH of a liquid in contact with the extended-gate ITO surface.
The use of dual-gated ISFETs for increased sensitivity is described in Go, J., Nair, P., Reddy, B., Dorvel, B., Bashir, R. and Alam, M., “Coupled Heterogeneous Nanowire-Nanoplate Planar Transistor Sensors for Giant (>10 V/pH) Nernst Response.” ACS Nano, 6(7), pp. 5972-5979 (2012). A Si nanoplate-nanowire transistor pair is used as a dual-gate ISFET where changes in pH are determined by sweeping the gate voltage and measuring the IV response. Changes in potential at the nanoplate require larger shifts in potential at the nanowire in order to maintain the same current. In this way, the signal from the sensing of the nanoplate is amplified.
U.S. Pat. No. 8,415,716 (Rothberg et al., issued Apr. 9, 2013) describes improved array control and ISFET pixel designs facilitating increased measurement sensitivity and accuracy while allowing small pixel sizes and large arrays. Improvements are made upon the ISFET array designs of Milgrew et al. ISFET measurement linearity and dynamic range is sacrificed in order to relax the requirement for both n- and p-type transistors, reducing pixel complexity and size. Therefore, large dense arrays are possible, but measurement range is limited. Array control circuits are also disclosed including analogue-to-digital conversion on the same integrated circuit as the array but located outside of the sensor array region. In general, Rothberg et al. describes methods for signal processing in order to improve the signal to noise ratio rather than signal amplification, no in-pixel amplification of sensor signal.
US2005/0230271 (Levon et al., published Oct. 20, 2005) discloses an active matrix array of floating gate ISFETs. Sensing is performed by detection of the threshold voltage of two ISFETs, one of which is coated with a sensing material. The difference signal between the two ISFETs is amplified to give the output signal.
US2013/0200438 (Liu et al., published Aug. 8, 2013) describes the use of various dual-gate ISFETs for signal amplification in the detection of biomolecules at a sensing surface.
U.S. Pat. No. 8,247,849 (Fife et al., issued Aug. 21, 2012) describes a two transistor pixel circuit for forming an array of ISFETs.
U.S. Pat. No. 8,741,680 (Fife et al., issued Jun. 3, 2014) discloses further details for two transistor pixel circuits and explicitly describes active matrix implementation.
U.S. Pat. No. 8,940,569 (Bedell et al., issued Jan. 27, 2015) discloses a dual-gate ISFET operated in a constant current mode with amplification by means of an operational-amplifier based circuit. The possible use of such architecture as a pixel within an array is referred to, but no pixel circuit for such an implementation is shown.